Editors' ChoiceCancer

TrkB Promotes Metastases

STKE  31 Aug 2004:
Vol. 2004, Issue 248, pp. tw309
DOI: 10.1126/stke.2482004tw309

In a screen for proteins that would prevent rat intestinal epithelial cell death caused by loss of cell attachment, so-called anoikis, Douma et al. identified the neurotrophin receptor tyrosine kinase TrkB. Further analysis showed that overexpression of TrkB with or without coexpression of its ligand, brain-derived neurotrophic factor (BDNF), prevented apoptosis in response to transfer of cells from an attached culture condition to a detached culture condition. Furthermore, engineered cells expressing luciferase (to allow noninvasive imaging) and TrkB with or without coexpression of BDNF were highly metastatic and tumorigenic when injected (subcutaneously or intravenously) into nude mice. TrkB appeared to mediate its cell survival effects by stimulating the phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB) pathways. However, the downstream effectors remain unknown. Inhibition of mTOR (mammalian target of rapamycin), Rac, or mitogen and extracellular signal-regulated protein kinase (MEK) failed to block the survival effects of TrkB. The implications of these results for cancer therapy and prognosis are discussed by Liotta and Kohn.

S. Douma, T. Van Laar, J. Zevenhoven, R. Meuwissen, E. Van Garderen, D. S. Peeper, Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430, 1034-1039 (2004). [Online Journal]

L. A. Liotta, E. Kohn, Anoikis: Cancer and the homeless cell. Nature 430, 973-974 (2004). [Online Journal]